chr3-51712765-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000839.5(GRM2):c.743C>T(p.Ala248Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,613,348 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 9 hom. )

Consequence

GRM2
NM_000839.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.34

Publications

7 publications found

Variant links:

Genes affected

GRM2 (HGNC:4594): (glutamate metabotropic receptor 2) L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]

GRM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042814016).

BP6

Variant 3-51712765-C-T is Benign according to our data. Variant chr3-51712765-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 737829.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 326 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000839.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRM2	NM_000839.5	MANE Select	c.743C>T	p.Ala248Val	missense	Exon 3 of 6	NP_000830.2	Q14416
GRM2	NM_001349117.2		c.-607C>T		5_prime_UTR	Exon 3 of 7	NP_001336046.1
GRM2	NM_001349116.2		c.-138-254C>T		intron	N/A	NP_001336045.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRM2	ENST00000395052.8	TSL:2 MANE Select	c.743C>T	p.Ala248Val	missense	Exon 3 of 6	ENSP00000378492.3	Q14416
GRM2	ENST00000296479.9	TSL:1	n.743C>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000296479.5	H7BXL3
GRM2	ENST00000464585.1	TSL:1	n.2422C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

326

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00323

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00220

AC:

550

AN:

249848

AF XY:

0.00207

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00580

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00385

Gnomad NFE exome

AF:

0.00325

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00252

AC:

3685

AN:

1460994

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1743

AN XY:

726794

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33480

American (AMR)

AF:

0.000581

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00693

AC:

181

AN:

26130

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00441

AC:

232

AN:

52566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00278

AC:

3094

AN:

1112000

Other (OTH)

AF:

0.00232

AC:

140

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

249

498

748

997

1246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00214

AC:

326

AN:

152354

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41574

American (AMR)

AF:

0.000849

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00806

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00301

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00323

AC:

220

AN:

68036

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00280

Hom.:

Bravo

AF:

0.00182

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00231

AC:

281

EpiCase

AF:

0.00289

EpiControl

AF:

0.00255

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.31

M_CAP

Benign

0.060

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.81

PhyloP100

2.3

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

REVEL

Benign

0.17

Sift

Benign

0.10

Sift4G

Benign

0.28

Polyphen

0.051

Vest4

0.078

MVP

0.40

MPC

0.59

ClinPred

0.012

GERP RS

4.4

Varity_R

0.10

gMVP

0.44

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over